Neurogenesis in the vertebrate neural tube

Neurogenesis is the developmental process that generates neurons. Since all the cells, including neurons, are ultimately derived from a single cell, the fertilized egg, a complete account of neurogenesis involves understanding the processes that underlie both the proliferative events that produce neuron progenitors, as well as the events that regulate the withdrawal of cells from the proliferative cell cycle. In the developing vertebrate neural tube, both cell proliferation and withdrawal from the cell cycle are patterned in time and space. Thus, developmental processes that regulate neurogenesis necessarily intersect at one or more levels with those processes that pattern the neural tube. This conclusion was also apparent to Viktor Hamburger more than one half century ago when he wrote ‘Any discussion of the problems of regional and topographic determination, ..., must include the determination of mitotic patterns, which preceded and are basic to the patterns of differentiation’ (Hamburger and Levi-Montalcini, 1950). Much progress has been made in recent years about the basic molecular machinery that controls the cell cycle, including cells that proliferate in the vertebrate neural epithelium. Nevertheless, some basic questions remain; How is proliferation regulated in neuronal precursors? When and how do progenitor cells ‘decide’ to withdraw from the proliferative cycle? Do environmental cues regulate proliferative behavior, or is there evidence that withdrawal from the cell cycle is controlled by an underlying clock-like mechanism? Does the decision to withdraw from the cycle require changes in the orientation of the mitotic spindle? Since neurons are a diverse population of post-mitotic cells, varying with respect to a number of phenotypic characteristics including the location, size and shape, neurotransmitter and projection patterns; we also want to understand how those characteristics are related to the processes of neurogenesis per se. For example, when during neurogenesis is a phenotypic character specified? To what extent is cell fate specified prior to withdrawal from the proliferative cell cycle? Are the events that regulate neuronal differentiation initiated only after a cell withdraws from the cycle? What cues and molecular pathways might regulate these processes? This essay will address the questions focusing on the cells generated in the ventricular epithelium of the vertebrate neural tube, contrasting our knowledge about these events in the spinal cord of birds and mammals, with what is known about other regions of the neural tube.